Lysine-based amino-functionalized lipids for gene transfection: the influence of the chain composition on 2D properties

Abstract

The influence of the chain composition on the physical-chemical properties will be discussed for five transfection lipids containing the same lysine-based head group. For this purpose, the chain composition will be gradually varied from saturated tetradecyl (C) and hexadecyl (C) chains to longer but unsaturated oleyl (C) chains with double bonds in the cis configuration. In this work, we investigated the lipids as Langmuir monolayers at the air-water-interface in the absence and presence of calf thymus DNA applying different techniques such as infrared reflection absorption spectroscopy (IRRAS) and grazing incidence X-ray diffraction (GIXD). The replacement of saturated tetradecyl (C) and hexadecyl (C) chains by unsaturated oleyl (C) chains increases the fluidity of the lipid monolayer: TH10 < TT10 < OH10 < OT10 < OO10 resulting in a smaller packing density. TH10 forms the stiffest and OO10 the most fluid monolayer in this structure-property study. OO10 has a higher protonation degree compared to the saturated lipids TT10 and TH10 as well as to the hybrids OT10 and OH10 because of a better accessibility of the amine groups. Depending on the bulk pH, different scenarios of DNA coupling to the lipid monolayers have been proposed.

Lysine-based amino-functionalized lipids for gene transfection: 3D phase behaviour and transfection performance

“…41 For TH10 and OH10, the peptide-mimicking character has been already found by grazing incidence X-ray diffraction (GIXD) at the air-water interface. 3 Furthermore, hydrogen bonds and the Ca-Ca spacing have been found in WAXS for the very similar lipid TH4. 42 The only structural difference between TH10 and TH4 is the spacer group.…”

“…Grazing incidence X-ray diffraction experiments using monolayers of the investigated lipids indicate a head group lattice based on hydrogen bonds. 3 SAXS and WAXS measurements of OO10, OH10 and TH10 in bromide containing buffer at pH 10 were successfully performed (see Fig. 5C and D).…”

“…The fluidity increases with shorter chains and double bonds: TH10 o TT10 o OH10 o OT10 o OO10, a behaviour also described in monolayer experiments. 3 Additionally, a hydrogen bond network was found for the pure cationic lipids. The increasing volume of the chain domain changed the molecular shape such that TT10, TH10, OT10 and OH10 are cylinder-like while OO10 has an inverted cone-like molecular shape.…”

“…This work is the continuation of our previous investigations using five lipids containing different alkyl chain patterns but the same small head group type 10 in 2D model systems (Langmuir monolayers). 3 TT10, TH10, OT10, OH10 and OO10 are lysine-based aminofunctionalized peptide-mimicking lipids, which were synthesised as non-viral carriers for gene transfection (Fig. 1).…”

Cationic amphiphiles based on malonic acid amides as transfection mediators

“…Эти методы обеспечивают доставку полинуклеотидов в биологическую ткань или клетки -так называемую трансфекцию генов. Из-за деградации под действием нуклеаз «чистая» ДНК или РНК не может проникнуть через клеточную мембрану без использования физических методов, таких как инъекции или «генная пушка», поэтому необходимы носители, которые могли бы транспортировать ДНК через кровоток и эффективно высвобождать генетический материал вблизи клеточного ядра [3].…”